The isolation and chemical characterization of cell surface antigens of human thymus derived lymphocytes will enhance our understanding of the differentiative pathway of T cell lineage. In addition, the information obtained from such studies will provide a more precise understanding of the molecular events involved in the development of malignant cells derived from human thymocytes. The intention of the proposed studies is to utilize monoclonal reagents anti-T3, anti-T4 and anti-T5, which are specifically reactive with functionally distinct T cell subsets, for isolation and characterization of cell surface antigens. Differentiation antigens which are associated with the T helper/inducer subset (T3 plus, T4 plus, T5 minus) are likely to be molecules that mediate the specific functions of those cells which display them. Similarly we believe that the differentiation markers on the T cell subset programmed for the suppressor/cytotoxic functions (T3 plus, T4 minus, T5 plus) may play a role in the effector phase of the immune response. Clearly, purified, well characterized cell surface antigens T3, T4 and T5, in addition to new sets of monoclonal antibodies specific for these antigens, would be required for the molecular dissection of such functions. A study of the structural heterogeneity of these antigens in the human population would determine the extent of a genetic polymorphism. Lastly, a chemical description of the T cell subset markers would be of paramount importance for future studies of the molecular genetics of T cell differentiation. It is our belief that a more detailed knowledge of the T cell surface will result in a deeper understanding of the function of these in the immune response.